MIF: Macrophage Migration Inhibitory Factor

A pleiotropic cytokine and enzyme involved in inflammation, immune regulation, and cancer.

Gene Information Card

Symbol MIF
Full Name Macrophage Migration Inhibitory Factor (glycosylation-inhibiting factor)
Gene Type protein-coding
Chromosomal Location 22q11.23
NCBI Gene ID 4282 ncbi.nlm.nih.gov/gene/4282
Ensembl ID ENSG00000240972
UniProt ID P14174
OMIM ID 153620
HGNC ID 7097
Aliases GIF, GLIF, MMIF

Description

The MIF gene encodes a pleiotropic cytokine and enzyme that plays a critical role in innate and adaptive immunity. It inhibits random macrophage migration, promotes pro-inflammatory cytokine production, and has tautomerase and oxidoreductase activities. MIF is involved in inflammatory diseases, autoimmune disorders, and cancer progression.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Rheumatoid Arthritis MIF promotes synovial inflammation and macrophage activation via CD74/CD44 signaling. NCBI Gene, OMIM
Sepsis Elevated MIF levels correlate with severity; MIF inhibits glucocorticoid anti-inflammatory effects. NCBI Gene, OMIM
Cancer (e.g., breast, lung, colorectal) MIF supports tumor growth, angiogenesis, and metastasis through MAPK and PI3K/Akt pathways. COSMIC, NCBI Gene
Inflammatory Bowel Disease MIF contributes to mucosal inflammation and macrophage infiltration. OMIM, NCBI Gene
Atherosclerosis MIF promotes monocyte adhesion and foam cell formation. NCBI Gene

Expression Profile

Tissue Expression
Tissue nTPM level
Lung 12.5 Medium
Spleen 10.2 Medium
Liver 8.7 Medium
Kidney 7.3 Low
Brain 4.1 Low
Cell Line Expression
Cell Line nTPM Notes
HeLa 15.3 Cervical adenocarcinoma
A549 12.8 Lung carcinoma
MCF7 9.6 Breast adenocarcinoma
HepG2 8.4 Hepatocellular carcinoma
THP-1 20.1 Monocytic leukemia
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
rs755622 (G>C) SNP ~20% (global) Promoter variant; associated with increased MIF expression and susceptibility to inflammatory diseases.
rs5844572 (CATT repeat) Microsatellite Variable 5-8 CATT repeats in promoter; longer repeats linked to higher expression and disease risk.
p.Pro2Ser Missense <1% Reduced tautomerase activity; potential loss-of-function.
Mutation functional classification

Loss of Function (LOF)

Rare missense variants (e.g., p.Pro2Ser) reduce enzymatic activity and cytokine function.

Gain of Function (GOF)

Promoter polymorphisms (e.g., rs755622, high-repeat CATT) increase MIF expression, enhancing pro-inflammatory and tumorigenic effects.

Dominant Negative (DN)

Not reported for MIF.

Gene Ontology (GO)

• cytokine activity • tautomerase activity
• oxidoreductase activity • macrophage migration inhibitory factor activity
• protein homodimerization activity • extracellular space
• cytoplasm • nucleus
• inflammatory response • positive regulation of tumor necrosis factor production

Pathways

• Toll-like receptor signaling pathway
• MAPK signaling pathway
• PI3K-Akt signaling pathway
• Glucocorticoid receptor signaling
• CD74 signaling

Protein Summary

MIF is a 12.5 kDa protein that forms a homotrimer. It possesses tautomerase and oxidoreductase activities, though its primary biological function is as a pro-inflammatory cytokine. MIF binds to CD74 and CD44 receptors, activating ERK1/2, PI3K/Akt, and NF-κB pathways. It counter-regulates glucocorticoid immunosuppression and promotes cell survival, proliferation, and migration.

Related Products

Product name Cat.No. Species Gene ID
MIF4GD Knockout HEK293 Cell Line EDJ-KQ14265 Human 57409 Details Get a Quote
MIF Knockout HEK293 Cell Line EDJ-KQ50093 Human 4282 Details Get a Quote
MIF4GD Knockout A-549 Cell Line EDJ-KQ44281 Human 57409 Details Get a Quote
MIF4GD Knockout HCT 116 Cell Line EDJ-KQ44282 Human 57409 Details Get a Quote
MIF4GD Knockout HeLa Cell Line EDJ-KQ44283 Human 57409 Details Get a Quote
MIF Knockout MC-38 Cell Line EDJ-KZ349 Mouse 17319 Details Get a Quote
MIF Knockout HeLa Cell Line EDJ-KQ53873 Human 4282 Details Get a Quote
MIF Knockout A-549 Cell Line EDJ-KQ62363 Human 4282 Details Get a Quote
MIF Knockout HCT 116 Cell Line EDJ-KQ70833 Human 4282 Details Get a Quote
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